HeatSticks Not Such a Hot Solution to Tobacco-Related Disease

HeatSticks Not Such a Hot Solution to Tobacco-Related Disease

A US Food and Drug Administration (FDA) advisory committee has determined that a new “heat-not-burn” tobacco device does not definitively reduce the risk for tobacco-related disease, but does reduce exposure to harmful or potentially harmful chemicals.

The Tobacco Products Scientific Advisory Committee spent 2 days weighing data on the IQOS system, which was submitted by the manufacturer, Philip Morris International (PMI). It is not an electronic cigarette. Rather, it relies on a heating mechanism to aerosolize tobacco for inhalation.

The panel was charged with determining whether the company could sell the IQOS system — provided it is approved by the FDA in a separate marketing review process — with claims that it reduces the risk for disease or the risk for harm for smokers who exclusively use the new device. The reduced-risk language would appear on packaging, labels, and promotions and would replace the current surgeon general’s warnings.

Philip Morris — the world’s largest tobacco company — said it is seeking to move all of its sales to smoke-free products. It said that IQOS could help current smokers reduce their exposure to harmful chemicals and carcinogens and that it could cut tobacco-related deaths by 90,000 during the next 2 decades.

Some 40 million Americans currently smoke, said the company.

The FDA advisory committee were unanimous that the company had not proven that IQOS reduces the risk for tobacco-related diseases. But four of the nine voting members said PMI had presented data to support its claim that a complete switch to IQOS was associated with less risk for harm than continuing to smoke cigarettes. Five others said the company had not clearly demonstrated that possibility.

Overall, the committee seemed enthusiastic about the potential for IQOS to reduce smoking-related harms, but sounded a note of caution about many issues, including whether the perception that it is less risky and that its iPhone-like design might entice adolescents to start smoking, as well as the fact that IQOS users might continue to smoke cigarettes.

“I think what we’re trying to balance is the communication that these devices have less risk than combustible cigarettes, but they have more risk than never smoking,” said committee member Laura J. Bierut, MD, alumni endowed professor of psychiatry, Washington University School of Medicine, St. Louis, Missouri.

“If you have someone who completely switches and uses these products, there is great potential,” said panel chairman Philip Huang, MD, MPH, medical director and health authority, Austin/Travis County Health and Human Services Department, Texas. But, he added, “we need more information regarding initiation on youth, and appeal to youth. The experience with electronic cigarettes is very worrisome.”

Same Level of Nicotine

Committee member Michael Weitzman, MD, professor of pediatrics, New York University School of Medicine, New York City, also raised concerns that nicotine had been excluded from discussions of harm.

“There is an extensive literature that suggests that it is the gateway drug,” he said, adding that studies have shown that it primes addiction to opioids. “I do think we’re trivializing a big danger of the use of tobacco products,” he said.

Kris A. McLoughlin, DNP, APRN, a panelist from the office of the chief medical officer at the Substance Abuse and Mental Health Services Administration, agreed.

“I fear that people don’t understand the addictive properties of nicotine and might think that somehow because we’re talking decreased risk, we’re also talking decreased addiction related to nicotine,” said Dr McLoughlin.

The IQOS system “delivers roughly the same levels of nicotine as a combustible cigarette,” said Moira Gilchrist, PhD, vice president scientific and public communications for PMI. But the company noted repeatedly that IQOS is not an e-cigarette and that it is held to the same regulatory standards as combustible cigarettes.

For $80, a consumer would receive an iPhone-sized charger and a separate penlike device designed to hold HeatSticks, which contain a 300-mg tobacco plug — about half the tobacco in a cigarette. The HeatSticks — which are made of paper and come in packs — would be marketed under the Marlboro brand name.

The heating blade in the holder rises to 662° F, vaporizing the tobacco. A conventional cigarette burns tobacco at 1200° F. Although cigarette smoke contains some 4330 chemicals, the IQOS aerosol has just 750. Of those, three are unique, and 50 are present at higher levels than in a cigarette, said Manuel Peitsch, PhD, chief scientific officer at PMI.

IQOS is approved in 30 countries, and the company claims that 3.7 million people have switched from smoking to the device. The name IQOS means nothing and is not an acronym — it was simply an easy way to get a brand trademarked, said Dr Gilchrist.

The panel debated whether current American smokers would fully switch to IQOS or would continue to smoke while using the device, especially if they believed that using IQOS was less risky.

If individuals continued to smoke, that could negate any possible harm reduction, said the committee.

Company Wants to Stop Smoking

PMI cited data from postmarketing surveys in several countries that 50% to 70% of smokers reported useing IQOS exclusively. But the FDA said that in the company’s US study that mimicked real-world conditions, only 8% of individuals were still exclusively using IQOS at the end of 6 weeks, whereas 22.4% were using both IQOS and cigarettes.

PMI said it would be actively encouraging and helping consumers to fully embrace IQOS and stop smoking by setting up IQOS-only retail stores and providing an online and telephonic support system.

Still, three of the nine voting panelists said they saw a high likelihood of US smokers becoming dual users, and five rated it a medium possibility. Only one said it was a low possibility.

The committee was more fully convinced — voting 8 to 1 — that IQOS “significantly reduces your body’s exposure to harmful or potentially harmful chemicals.”

Overall, with IQOS, there was a 90% reduction in toxicants, said PMI. The FDA mostly confirmed PMI’s data, although its independent testing found higher levels of acrolein, formaldehyde, and benz(a)pyrene than reported by the company. But those levels were still significantly lower than in cigarettes: a greater than 90% reduction for acrolein and benzo(a)pyrene, and a greater than 77% reduction in formaldehyde.

But a majority of panel members said that the reduction in exposure to toxicants could not be “reasonably likely to translate to a measurable and substantial reduction in morbidity and/or mortality.”

In its pivotal human studies, PMI assessed six biomarkers of potential harm to determine whether the reduced exposure would result in biological changes that might indicate a change in long-term disease risk, especially for cardiovascular disease, chronic obstructive pulmonary disease, and lung cancer. PMI said that its studies showed movement in the right direction, but the FDA said the results were not substantially better than those of cigarette smokers.

The biomarkers “mostly went in the right direction towards less harm, but the changes were very small, and in most cases, not significant,” agreed panelist Stephen Hecht, PhD, Wallin Land Grant Professor of Cancer Prevention, University of Minnesota College of Pharmacy, Minneapolis.

Many panel members expressed concern that nonsmoking adolescents would be lured to IQOS by its design and novelty — especially given that IQOS sounds and looks like an Apple product.

PMI presented data on use in the United States by persons aged 18 to 25 years, who are of legal age to smoke, and on older adults. The company said — and the FDA concurred — that it was not appropriate to study tobacco products in anyone younger than 18.

The manufacturer also said that it will be restricted from marketing or promoting IQOS to children. And it said it will use well-validated age verification on its websites. It presented data from its US study that showed that among 18- to 25-year-old never-smokers, 1% to 3% said they were very likely to or would definitely try IQOS, even if it did not have a reduced-risk claim.

Seven percent to 10% said they were somewhat likely to try IQOS if it did not have a reduced-risk claim, and smaller percentages said they were likely to try it if the device was promoted as less risky.

The FDA concluded that the claim of lower risk did not increase young adult never-smokers’ intentions to try IQOS. The agency also noted that, unlike e-cigarettes, IQOS will not contain any special flavoring, aside from menthol.

But because PMI did not present any data on persons younger than 18 years, some panel members said they were not convinced that there would not be unintended use. They said they would look to the experience with e-cigarettes, in which there was rapid uptake among youth, as the closest comparator.

Two committee members said they believed there was a high risk of young never-smokers initiating use with IQOS; one said there was a medium likelihood; four said the likelihood was low; and two abstained, citing an absence of data.

Lower Risk Alternative

Panelist Robin J. Mermelstein, PhD, said she believed only a small number of persons would start using the product. “I think there will be a lot of boundaries in place,” said Dr Mermelstein, professor of psychology and director, Institute for Health Research and Policy, University of Illinois at Chicago, noting the high price and the company’s stated intentions to limit access.

A large number of speakers at the public hearing — most representing free-market and libertarian organizations and the vaping industry — said they supported availability of IQOS as a lower-risk alternative to smoking.

Several speakers representing LBGT groups also argued for its approval, noting that the population has higher rates of smoking and its related harms. Tobacco-related diseases kill 30,000 LGBT Americans annually, said Gregory Angelo, president of the Washington, DC–based Log Cabin Republicans.

The group “implores you to consider the value of IQOS heating products as vehicles that encourage smoking cessation and step down alternatives to traditional cigarettes,” said Angelo. It was not clear whether the group receives support from PMI. Angelo did not disclose any potential conflicts of interest.

Similarly, Erika Bliss, MD, a primary care physician, who also made no disclosures, said that she supported IQOS. “It would be such a great tool to have in my toolbox,” said Dr Bliss, who noted that many of her patients try to quit but can’t.

The FDA will now weigh both PMI’s application for marketing approval and its application to sell IQOS as a reduced-risk product.

The committee discussion, the votes, the company data, and public comment will be taken “into consideration as we think about the decision that we have to make,” said Mitchell Zeller, director of the FDA’s Center for Tobacco Products.

Altria Group Inc will sell IQOS in the United States under a licensing agreement with PMI. The FDA is expected to make a decision on the marketing application this year. It’s not clear when the agency would act on the risk-reduction application.

IQOS could be marketed even if the agency does not approve PMI’s claim that it is less risky than smoking.

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